Trial Outcomes & Findings for Pilot Ipilimumab in Stage IV Melanoma Receiving Palliative Radiation Therapy (NCT NCT01449279)

Last Updated: 2020-03-02

Results Overview

Serious adverse events (SAEs) defined as untoward medical occurrence that at any dose: results in death, is life-threatening (defined as an event in which the subject was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe), requires in subject hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event (defined as a medical event(s) that may not be immediately life-threatening or result in death or hospitalization but, may jeopardize the subject or may require intervention to prevent one of the other serious outcomes listed in the definition above.)

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

22 participants

Primary outcome timeframe

4 months

Results posted on

2020-03-02

Participant Flow

Subjects were recruited during clinic visits at the Stanford Cancer Center clinic. Subjects were informed of all options and given time to ask questions before signing consent in a private room.

Participant milestones

Participant milestones
Measure	Ipilimumab Treatment + Radiation Therapy Ipilimumab (BMS-734016, MDX010, MDX-CTLA4, Yervoy) will be administered as standard of care with base dose of 3 mg/kg iv over approximately 90 minutes every 3 weeks for a total of 4 treatments. Palliative radiation therapy to 1-2 sites of disease will start within 5 days of the first ipilimumab dose. Subjects will have follow up visits 2-4 weeks after the last ipilimumab dose and then every 3 months (±2 weeks) thereafter until progression of disease. Ipilimumab: Ipilimumab will be administered as a single agent standard of care with base dose of 3 mg/kg iv over approximately 90 minutes every 3 weeks for a total of 4 treatments. Radiation Therapy: Standard of care palliative radiation therapy will start within 5 days of the first ipilimumab dose. Dose is dependent upon lesion size and is determined by the radiation oncologist.
Overall Study STARTED	22
Overall Study COMPLETED	15
Overall Study NOT COMPLETED	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Ipilimumab Treatment + Radiation Therapy Ipilimumab (BMS-734016, MDX010, MDX-CTLA4, Yervoy) will be administered as standard of care with base dose of 3 mg/kg iv over approximately 90 minutes every 3 weeks for a total of 4 treatments. Palliative radiation therapy to 1-2 sites of disease will start within 5 days of the first ipilimumab dose. Subjects will have follow up visits 2-4 weeks after the last ipilimumab dose and then every 3 months (±2 weeks) thereafter until progression of disease. Ipilimumab: Ipilimumab will be administered as a single agent standard of care with base dose of 3 mg/kg iv over approximately 90 minutes every 3 weeks for a total of 4 treatments. Radiation Therapy: Standard of care palliative radiation therapy will start within 5 days of the first ipilimumab dose. Dose is dependent upon lesion size and is determined by the radiation oncologist.
Overall Study Lack of Efficacy	5
Overall Study Toxicity	2

Baseline Characteristics

Pilot Ipilimumab in Stage IV Melanoma Receiving Palliative Radiation Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ipilimumab Treatment + Radiation Therapy n=22 Participants Ipilimumab (BMS-734016, MDX010, MDX-CTLA4, Yervoy) will be administered as standard of care with base dose of 3 mg/kg iv over approximately 90 minutes every 3 weeks for a total of 4 treatments. Palliative radiation therapy to 1-2 sites of disease will start within 5 days of the first ipilimumab dose. Subjects will have follow up visits 2-4 weeks after the last ipilimumab dose and then every 3 months (±2 weeks) thereafter until progression of disease. Ipilimumab: Ipilimumab will be administered as a single agent standard of care with base dose of 3 mg/kg iv over approximately 90 minutes every 3 weeks for a total of 4 treatments. Radiation Therapy: Standard of care palliative radiation therapy will start within 5 days of the first ipilimumab dose. Dose is dependent upon lesion size and is determined by the radiation oncologist.
Age, Continuous	59 Years n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants
Region of Enrollment United States	22 participants n=5 Participants

PRIMARY outcome

Timeframe: 4 months

Population: All subjects.

Outcome measures

Outcome measures
Measure	Ipilimumab Treatment + Radiation Therapy n=22 Participants Ipilimumab (BMS-734016, MDX010, MDX-CTLA4, Yervoy) will be administered as standard of care with base dose of 3 mg/kg iv over approximately 90 minutes every 3 weeks for a total of 4 treatments. Palliative radiation therapy to 1-2 sites of disease will start within 5 days of the first ipilimumab dose. Subjects will have follow up visits 2-4 weeks after the last ipilimumab dose and then every 3 months (±2 weeks) thereafter until progression of disease. Ipilimumab: Ipilimumab will be administered as a single agent standard of care with base dose of 3 mg/kg iv over approximately 90 minutes every 3 weeks for a total of 4 treatments. Radiation Therapy: Standard of care palliative radiation therapy will start within 5 days of the first ipilimumab dose. Dose is dependent upon lesion size and is determined by the radiation oncologist.
Safety Measurement - Percentage of Patients Experiencing Serious Adverse Events (SAEs) in the First 4 Months of Treatment.	9 Participants

SECONDARY outcome

Timeframe: 2 to 4 weeks after last ipilimumab dose then every 3 months +/- 2 weeks until progression of disease

Population: All subjects.

Compare tumor response rate and duration of response at unirradiated sites in patients with Stage IV melanoma with historical controls. Response assessed per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by physical measurement; magnetic resonance imaging (MRI); computed tomography (CT), positron emission tomography (PET)-CT; and/or X-rays: * Complete Response (CR) = Disappearance of all target lesions * Partial Response (PR) = ≥ 30% decrease in the sum of the longest diameter of target lesions * Overall Response (OR) = CR + PR

Outcome measures

Outcome measures
Measure	Ipilimumab Treatment + Radiation Therapy n=22 Participants Ipilimumab (BMS-734016, MDX010, MDX-CTLA4, Yervoy) will be administered as standard of care with base dose of 3 mg/kg iv over approximately 90 minutes every 3 weeks for a total of 4 treatments. Palliative radiation therapy to 1-2 sites of disease will start within 5 days of the first ipilimumab dose. Subjects will have follow up visits 2-4 weeks after the last ipilimumab dose and then every 3 months (±2 weeks) thereafter until progression of disease. Ipilimumab: Ipilimumab will be administered as a single agent standard of care with base dose of 3 mg/kg iv over approximately 90 minutes every 3 weeks for a total of 4 treatments. Radiation Therapy: Standard of care palliative radiation therapy will start within 5 days of the first ipilimumab dose. Dose is dependent upon lesion size and is determined by the radiation oncologist.
Response Rate	11 Participants

SECONDARY outcome

Timeframe: 2 to 4 weeks after last ipilimumab dose then every 3 months +/- 2 weeks until progression of disease

Population: All subjects

Median time to overall survival was calculated using the Kaplan-Meier algorithm.

Outcome measures

Outcome measures
Measure	Ipilimumab Treatment + Radiation Therapy n=22 Participants Ipilimumab (BMS-734016, MDX010, MDX-CTLA4, Yervoy) will be administered as standard of care with base dose of 3 mg/kg iv over approximately 90 minutes every 3 weeks for a total of 4 treatments. Palliative radiation therapy to 1-2 sites of disease will start within 5 days of the first ipilimumab dose. Subjects will have follow up visits 2-4 weeks after the last ipilimumab dose and then every 3 months (±2 weeks) thereafter until progression of disease. Ipilimumab: Ipilimumab will be administered as a single agent standard of care with base dose of 3 mg/kg iv over approximately 90 minutes every 3 weeks for a total of 4 treatments. Radiation Therapy: Standard of care palliative radiation therapy will start within 5 days of the first ipilimumab dose. Dose is dependent upon lesion size and is determined by the radiation oncologist.
Overall Survival	107 weeks Interval 7.0 to 214.0

SECONDARY outcome

Timeframe: 2 to 4 weeks after last ipilimumab dose then every 3 months +/- 2 weeks until progression of disease

Population: all subjects

The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The duration of overall CR is measured from the time measurement criteria are first met for CR until the first date that progressive disease is objectively documented.

Outcome measures

Outcome measures
Measure	Ipilimumab Treatment + Radiation Therapy n=3 Participants Ipilimumab (BMS-734016, MDX010, MDX-CTLA4, Yervoy) will be administered as standard of care with base dose of 3 mg/kg iv over approximately 90 minutes every 3 weeks for a total of 4 treatments. Palliative radiation therapy to 1-2 sites of disease will start within 5 days of the first ipilimumab dose. Subjects will have follow up visits 2-4 weeks after the last ipilimumab dose and then every 3 months (±2 weeks) thereafter until progression of disease. Ipilimumab: Ipilimumab will be administered as a single agent standard of care with base dose of 3 mg/kg iv over approximately 90 minutes every 3 weeks for a total of 4 treatments. Radiation Therapy: Standard of care palliative radiation therapy will start within 5 days of the first ipilimumab dose. Dose is dependent upon lesion size and is determined by the radiation oncologist.
Duration of Complete Response	112 weeks Interval 60.0 to 139.0

SECONDARY outcome

Timeframe: 2 to 4 weeks after last ipilimumab and then every 3 months until disease progression.

Population: all patients that did not have SAEs during treatment and did not have complete response.

Length of time between first dose of ipilimumab and a partial response according to RECIST v1.1 (see above) and immune response criteria

Outcome measures

Outcome measures
Measure	Ipilimumab Treatment + Radiation Therapy n=3 Participants Ipilimumab (BMS-734016, MDX010, MDX-CTLA4, Yervoy) will be administered as standard of care with base dose of 3 mg/kg iv over approximately 90 minutes every 3 weeks for a total of 4 treatments. Palliative radiation therapy to 1-2 sites of disease will start within 5 days of the first ipilimumab dose. Subjects will have follow up visits 2-4 weeks after the last ipilimumab dose and then every 3 months (±2 weeks) thereafter until progression of disease. Ipilimumab: Ipilimumab will be administered as a single agent standard of care with base dose of 3 mg/kg iv over approximately 90 minutes every 3 weeks for a total of 4 treatments. Radiation Therapy: Standard of care palliative radiation therapy will start within 5 days of the first ipilimumab dose. Dose is dependent upon lesion size and is determined by the radiation oncologist.
Duration of Partial Response.	40 weeks Interval 29.0 to 53.0

SECONDARY outcome

Timeframe: 2 to 4 weeks after last ipilimumab and then every 3 months until disease progression.

Population: All patients who did not have SAEs during treatment and did not reach complete response or partial response.

Stable disease is measured from the start of the treatment until the criteria for progression are met, taking as reference the smallest measurements recorded since the treatment started, including the baseline measurements

Outcome measures

Outcome measures
Measure	Ipilimumab Treatment + Radiation Therapy n=5 Participants Ipilimumab (BMS-734016, MDX010, MDX-CTLA4, Yervoy) will be administered as standard of care with base dose of 3 mg/kg iv over approximately 90 minutes every 3 weeks for a total of 4 treatments. Palliative radiation therapy to 1-2 sites of disease will start within 5 days of the first ipilimumab dose. Subjects will have follow up visits 2-4 weeks after the last ipilimumab dose and then every 3 months (±2 weeks) thereafter until progression of disease. Ipilimumab: Ipilimumab will be administered as a single agent standard of care with base dose of 3 mg/kg iv over approximately 90 minutes every 3 weeks for a total of 4 treatments. Radiation Therapy: Standard of care palliative radiation therapy will start within 5 days of the first ipilimumab dose. Dose is dependent upon lesion size and is determined by the radiation oncologist.
Stable Disease	39 weeks Interval 26.0 to 76.0

SECONDARY outcome

Timeframe: 2 to 4 weeks after last ipilimumab and then every 3 months until disease progression.

Population: All patients who had either a complete response or partial response.

Time from the first dose of ipilimumab to the first tumor measurement showing either a complete or partial response to therapy.

Outcome measures

Outcome measures
Measure	Ipilimumab Treatment + Radiation Therapy n=6 Participants Ipilimumab (BMS-734016, MDX010, MDX-CTLA4, Yervoy) will be administered as standard of care with base dose of 3 mg/kg iv over approximately 90 minutes every 3 weeks for a total of 4 treatments. Palliative radiation therapy to 1-2 sites of disease will start within 5 days of the first ipilimumab dose. Subjects will have follow up visits 2-4 weeks after the last ipilimumab dose and then every 3 months (±2 weeks) thereafter until progression of disease. Ipilimumab: Ipilimumab will be administered as a single agent standard of care with base dose of 3 mg/kg iv over approximately 90 minutes every 3 weeks for a total of 4 treatments. Radiation Therapy: Standard of care palliative radiation therapy will start within 5 days of the first ipilimumab dose. Dose is dependent upon lesion size and is determined by the radiation oncologist.
Median Time to Complete Response or Partial Response	19 weeks Interval 12.0 to 52.0

SECONDARY outcome

Timeframe: 2 to 4 weeks after last ipilimumab and then every 3 months until disease progression.

Population: All subject who did not have SAEs during treatment.

Median time to progression-free survival (PFS) was calculated using the Kaplan-Meier algorithm

Outcome measures

Outcome measures
Measure	Ipilimumab Treatment + Radiation Therapy n=20 Participants Ipilimumab (BMS-734016, MDX010, MDX-CTLA4, Yervoy) will be administered as standard of care with base dose of 3 mg/kg iv over approximately 90 minutes every 3 weeks for a total of 4 treatments. Palliative radiation therapy to 1-2 sites of disease will start within 5 days of the first ipilimumab dose. Subjects will have follow up visits 2-4 weeks after the last ipilimumab dose and then every 3 months (±2 weeks) thereafter until progression of disease. Ipilimumab: Ipilimumab will be administered as a single agent standard of care with base dose of 3 mg/kg iv over approximately 90 minutes every 3 weeks for a total of 4 treatments. Radiation Therapy: Standard of care palliative radiation therapy will start within 5 days of the first ipilimumab dose. Dose is dependent upon lesion size and is determined by the radiation oncologist.
Progression-free Survival (PFS)	26 weeks Interval 9.0 to 50.0

Adverse Events

Ipilimumab Treatment + Radiation Therapy

Serious events: 11 serious events

Other events: 22 other events

Deaths: 13 deaths

Serious adverse events

Serious adverse events
Measure	Ipilimumab Treatment + Radiation Therapy n=22 participants at risk Ipilimumab (BMS-734016, MDX010, MDX-CTLA4, Yervoy) will be administered as standard of care with base dose of 3 mg/kg iv over approximately 90 minutes every 3 weeks for a total of 4 treatments. Palliative radiation therapy to 1-2 sites of disease will start within 5 days of the first ipilimumab dose. Subjects will have follow up visits 2-4 weeks after the last ipilimumab dose and then every 3 months (±2 weeks) thereafter until progression of disease. Ipilimumab: Ipilimumab will be administered as a single agent standard of care with base dose of 3 mg/kg iv over approximately 90 minutes every 3 weeks for a total of 4 treatments. Radiation Therapy: Standard of care palliative radiation therapy will start within 5 days of the first ipilimumab dose. Dose is dependent upon lesion size and is determined by the radiation oncologist.
Hepatobiliary disorders Pancreatitis	4.5% 1/22 • Number of events 1 • Collected form first dose of study drug until the end of active follow up.
Nervous system disorders Confusion	4.5% 1/22 • Number of events 1 • Collected form first dose of study drug until the end of active follow up.
Nervous system disorders Hemorrhage, CNS	4.5% 1/22 • Number of events 1 • Collected form first dose of study drug until the end of active follow up.
Gastrointestinal disorders Colitis	13.6% 3/22 • Number of events 3 • Collected form first dose of study drug until the end of active follow up.
Gastrointestinal disorders Nausea	18.2% 4/22 • Number of events 5 • Collected form first dose of study drug until the end of active follow up.
Blood and lymphatic system disorders Anemia	4.5% 1/22 • Number of events 1 • Collected form first dose of study drug until the end of active follow up.
Gastrointestinal disorders dehydration	4.5% 1/22 • Number of events 1 • Collected form first dose of study drug until the end of active follow up.
Gastrointestinal disorders Diarrhea	13.6% 3/22 • Number of events 3 • Collected form first dose of study drug until the end of active follow up.
Gastrointestinal disorders Enteritis	4.5% 1/22 • Number of events 1 • Collected form first dose of study drug until the end of active follow up.
Infections and infestations INFECTION-Other: Sepsis	4.5% 1/22 • Number of events 1 • Collected form first dose of study drug until the end of active follow up.
Infections and infestations INFECTION-Systemic Inflammatory Response Syndrome (SIRS)	4.5% 1/22 • Number of events 1 • Collected form first dose of study drug until the end of active follow up.
Gastrointestinal disorders Melena	4.5% 1/22 • Number of events 1 • Collected form first dose of study drug until the end of active follow up.
Nervous system disorders new brain lesion	4.5% 1/22 • Number of events 1 • Collected form first dose of study drug until the end of active follow up.
Gastrointestinal disorders PAIN-GASTROINTESTINAL-Abdomen NOS	18.2% 4/22 • Number of events 6 • Collected form first dose of study drug until the end of active follow up.
Gastrointestinal disorders Vomitting	18.2% 4/22 • Number of events 5 • Collected form first dose of study drug until the end of active follow up.

Other adverse events

Other adverse events
Measure	Ipilimumab Treatment + Radiation Therapy n=22 participants at risk Ipilimumab (BMS-734016, MDX010, MDX-CTLA4, Yervoy) will be administered as standard of care with base dose of 3 mg/kg iv over approximately 90 minutes every 3 weeks for a total of 4 treatments. Palliative radiation therapy to 1-2 sites of disease will start within 5 days of the first ipilimumab dose. Subjects will have follow up visits 2-4 weeks after the last ipilimumab dose and then every 3 months (±2 weeks) thereafter until progression of disease. Ipilimumab: Ipilimumab will be administered as a single agent standard of care with base dose of 3 mg/kg iv over approximately 90 minutes every 3 weeks for a total of 4 treatments. Radiation Therapy: Standard of care palliative radiation therapy will start within 5 days of the first ipilimumab dose. Dose is dependent upon lesion size and is determined by the radiation oncologist.
Gastrointestinal disorders Diarrhea	63.6% 14/22 • Number of events 20 • Collected form first dose of study drug until the end of active follow up.
General disorders Fatigue	68.2% 15/22 • Number of events 16 • Collected form first dose of study drug until the end of active follow up.
Gastrointestinal disorders Nausea	54.5% 12/22 • Number of events 17 • Collected form first dose of study drug until the end of active follow up.
Skin and subcutaneous tissue disorders Rash: Erythema	45.5% 10/22 • Number of events 13 • Collected form first dose of study drug until the end of active follow up.
Gastrointestinal disorders Vomiting	40.9% 9/22 • Number of events 13 • Collected form first dose of study drug until the end of active follow up.

Additional Information

Dr. Susan J Knox

Stanford Cancer Institute

Phone: 650-725-2720

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place